FUNCTION OF DOPAMINE IN THE PRIMATE SUBSTANTIA NIGRA

灵长类动物黑质中多巴胺的功能

• 批准号: 7715773
• 负责人: Thomas N Wichmann
• 金额: $ 3.56万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715773
• 关键词: Agonist; Anatomy; Animals; Antiparkinson Agents; Axon; Cell Nucleus; Computer Retrieval of Information on Scientific Projects Database; Dopamine; Dopamine Receptor; Electrons; Funding; Grant; Institution; Microscopic; Monkeys; Neurons; Neurotoxins; Parkinsonian Disorders; Primates; Property; Reporting; Research; Research Personnel; Resources; Source; Substantia nigra structure; United States National Institutes of Health; Work; animal data; base; insight; receptor; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During the reporting period, we investigated the effects of dopamine on neuronal activity and the distribution of dopamine receptors in the substantia nigra pars reticulata in normal and parkinsonian monkeys. Parkinsonism is produced by treatment with the dopaminergic neurotoxin MPTP. We completed our work on the effects of dopamine D1-like receptor (D1LR) agonists on the electrophysiologic activity of neurons in the substantia nigra pars reticulata (SNr) in MPTP-treated monkeys. This has now been studied in three animals. We found that D1LR agonists strongly inhibit SNr activity, and that they increase neuronal bursting and oscillatory activity in this nucleus. We have also begun to study the activity of D2-like receptor (D2LR) agonists and antagonists on SNr activity. Thus far, the experiments have been completed in one animal, but the data arer not yet analyzed. We have also prepared a second animal for these studies, and plan to study D2LR actions in at least one MPTP-treated animal in the next year. Finally, we have completed our electron microscopic studies on the distribution of D1LRs in the SNr, using material from seven normal and five MPTP-treated animals. These studies showed that D1LRs are located primarily in unmyelinated axons, but that a subtype of these receptors (D5-receptors) is also found postsynaptically. There were no significant differences between normal and parkinsonian animals. These studies provided insights into the anatomic basis and functional effects of nigral dopamine release in monkeys in the normal state and in parkinsonism. We have shown that functional D1LRs are present in the primate SNr, suggesting that therapies aimed at these receptors may have antiparkinsonian properties

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在报告期间，我们调查了多巴胺对正常和帕金森尼猴子的底虫nigra pars片段中多巴胺受体分布的影响。 帕金森病是通过多巴胺能神经毒素MPTP治疗产生的。 我们完成了关于多巴胺D1样受体（D1LR）激动剂对MPTP处理的猴子中Nigra pars网状（SNR）神经元电生理活性的影响的研究。 现在已经在三只动物中对此进行了研究。 我们发现D1LR激动剂强烈抑制SNR活性，并且它们会增加该核中神经元爆发和振荡活性。 我们还开始研究D2样受体（D2LR）激动剂和拮抗剂对SNR活性的活性。 到目前为止，实验已经在一只动物中完成，但是尚未分析数据。 我们还为这些研究准备了第二种动物，并计划在第二年研究至少一种经MPTP处理的动物的D2LR作用。 最后，我们使用了七种正常和五只MPTP处理的动物的材料完成了有关D1LR在SNR中D1LR分布的电子显微镜研究。 这些研究表明，D1LR主要位于不髓鞘的轴突中，但是这些受体（D5受体）的亚型也被发现后突触。 正常动物和帕金森氏动物之间没有显着差异。 这些研究提供了对正常状态和帕金森氏症中猴子多巴胺释放的解剖学基础和功能作用的见解。 我们已经表明，灵长类动物SNR中存在功能性D1LR，这表明针对这些受体的疗法可能具有反帕金森特性